Pluripotent stem cells such as human embryonic stem cells (hESCs) have the ability to differentiate into any of the three germ layers, giving rise to any adult cell type in the human body. This unique property provides a potential for developing new treatments for a number of serious cell degenerative diseases, such as diabetes, spinal chord injury, heart diseases and the like. In addition, cells derived from hESCs can be used for drug discovery and toxicology studies. Several groups have already demonstrated the differentiation of hESCs into different cell types. However, major obstacles in the development of such hESC-based treatments include (i) obtaining and maintaining adequate numbers of undifferentiated hESCs in cell and tissue culture and (ii) controlling their differentiation in order to produce specific cell types. Stem cell cultures, such as hESC cell cultures are typically seeded with a small number of cells from a cell bank or stock and then amplified in the undifferentiated state until differentiation is desired for a given therapeutic application. One current way to accomplish this is to culture the hESCs or their differentiated cells in the presence of surfaces and media containing animal-derived components, such as feeder layers, fetal bovine serum, or MATRIGEL™ available from BD Biosciences San Jose, Calif. These additions to the culture environment expose the cells to potentially harmful viruses or other infectious agents which could be transferred to patients or compromise general culture and maintenance of undifferentiated hESC. In addition, those biological culture products are also vulnerable to batch variation, immune response and limited shelf-life.
Synthetic surfaces have the potential to provide significant benefits to prevent the above concerns. However, the effects of synthetic surfaces on the behavior of stem cells, in particular, hESCs, have not been studied in great detail. Nanoliter-scale synthesis of arrayed synthetic biomaterials has been proposed for performing high throughput screening for hESC culture application. However, such small scale culture presents several problems. For example, due to the size of each spot in the array, the number of cells in each spot is limited and the corresponding cell response is questionable.
Problems also exist with regard to employing such screening systems on a larger scale, such as with traditional cell culture glass-ware or plastic-ware. For example, obtaining uniform, non-toxic surfaces for reliable culturing and screening can be difficult, particularly with polymeric mixtures having a high viscosity. For example, the high viscosity can reduce the speed at which surfaces may be produced, and thus may be too inefficient for high throughput screening. Further high viscosity fluids can result in non-uniform coatings on a large surface area, thereby hindering the ability to reliably determine cell responses.